The Effects of Chronic Intermittent Hypoxia in Bleomycin-Induced Lung Injury on Pulmonary Fibrosis via Regulating the NF-κB/Nrf2 Signaling Pathway.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with pulmonary fibrosis. Chronic intermittent hypoxia (CIH) is considered to be a surrogate of OSA. However, its exact role in pulmonary fibrosis remains uncertain. Therefore, we investigated the mechanism underlying CIH-induced pulmonary fibrosis and the role of the anti-fibrotic agent in bleomycin (BLE) induced lung injury. METHODS: Mice were divided into eight groups: the normoxia (NOR), CIH, NOR plus BLE, CIH plus BLE, NOR plus pirfenidone (PF), CIH plus PF, NOR plus BLE and PF, and CIH plus BLE and PF groups. BLE was administered intratracheally on day 14 following CIH or NOR exposure. Subsequently, the mice were exposed to CIH or NOR for an additional 4 weeks. PF was administered orally on day 5 after BLE instillation once daily for 3 weeks. RESULTS: In the BLE-treated groups, CIH-induced more collagen deposition in lung tissues than NOR, and significantly increased hydroxyproline and transforming growth factor-ß expression. The CIH and BLE-treated groups showed increased lung inflammation compared to NOR or CIH groups. Following CIH with BLE treatment, nuclear factor-κB (NF-κB) protein expression was significantly increased, whereas nuclear factor-erythroid-related factor 2 (Nrf2) and heme oxygenase-1 protein levels were decreased. After PF treatment, NF-κB and Kelch-like ECH-associated protein 1 expression were suppressed, and Nrf2 expression was increased. CONCLUSION: CIH accelerated lung fibrosis in BLE-induced lung injury in mice, potentially by regulating the NF-κB/Nrf2 signaling pathway. Our results implicate PF as a potential therapeutic agent for treating pulmonary fibrosis in individuals with OSA and idiopathic pulmonary fibrosis.

Blockade of thymic stromal lymphopoietin and CRTH2 attenuates airway inflammation in a murine model of allergic asthma.

BACKGROUND/AIMS: Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine that plays a key role in Th2-mediated inflammation, both directly by promoting the proliferation of naïve CD4 Th2 cells, and indirectly by activating dendritic cells (DCs). TSLP-activated DCs induce the expansion of chemoattractant receptor homologous molecule expressed on Th2 (CRTH2)+ CD4+ Th2 memory cells, which undergo a Th2 response and express prostaglandin D2 (PGD2) synthase. CRTH2, a PGD2 receptor, is a selective Th2-cell surface marker. We investigated the effects of an anti-TSLP antibody (Ab) and a CRTH2 antagonist, as well as their mechanisms of action, in a mouse model of acute asthma. METHODS: BALB/c mice were sensitized and challenged with ovalbumin. We then evaluated the effects of the administration of an anti-TSLP Ab either alone or together with a CRTH2 antagonist on cell counts, Th2 cytokine levels in bronchoalveolar fluid, and the levels of epithelium-derived cytokines such as TSLP, interleukin (IL) 33, and IL-25 in lung homogenates, as well as airway hyper-responsiveness (AHR). RESULTS: Anti-TSLP Ab and the CRTH2 antagonist significantly attenuated eosinophilic airway inflammation, AHR, and the expression of Th2 cytokines. The expression of GATA-3 and the levels of IL-33 and IL-25 in lung tissues were affected by the combined anti-TSLP and CRTH2 antagonist treatment. CONCLUSION: These results suggest that the dual blockade of TSLP and CRTH2 may serve as an effective treatment target for eosinophilic asthma.

Evaluation of Clinically Meaningful Changes in Measures of Frailty.

BACKGROUND: To determine the clinically meaningful changes and responsiveness of widely used frailty measures. METHODS: We analyzed data from a prospective cohort study of 1,135 community-dwelling older adults who underwent assessments of frailty and health-related quality of life using the EuroQol-5D at baseline and 1 year later. Frailty measures included deficit-accumulation frailty index (FI); frailty phenotype; Fatigue, Resistance, Ambulation, Illness, and Loss of Weight scale; and the Study of Osteoporotic Fracture (SOF) index. We determined the clinically meaningful changes by the distribution-based method and the anchor-based method using the EuroQol-5D score and responsiveness indices. RESULTS: Frailty measures were available in 925 participants at 1 year (81.5%). Based on the distribution-based method, small and large clinically meaningful changes were 0.019 and 0.057 for FI, 0.249 and 0.623 for frailty phenotype, 0.235 and 0.587 for FRAIL scale, and 0.116 and 0.289 for SOF index, respectively. The anchor-based estimates of small and large changes were 0.028 and 0.076 for FI, 0.097 and 0.607 for frailty phenotype, 0.269 and 0.368 for FRAIL scale, and 0.023 and 0.287 for SOF index, respectively. Based on the responsiveness index, per-group sample sizes to achieve 80% power in clinical trials, ranged from 51 (FI) to 7,272 (SOF index) for a small change and 9 (FI) to 133 (FRAIL scale) for a large change. CONCLUSIONS: The estimates of clinically meaningful change of frailty measures can inform the choice of frailty measures to track longitudinal changes of frailty in clinical trials and clinical care of community-dwelling older adults.

Estimating age-related changes in in vivo cerebral magnetic resonance angiography using convolutional neural network.

Although age-related changes of cerebral arteries were observed in in vivo magnetic resonance angiography (MRA), standard tools or methods measuring those changes were limited. In this study, we developed and evaluated a model to measure age-related changes in the cerebral arteries from 3D MRA using a 3D deep convolutional neural network. From participants without any medical abnormality, training (n = 800) and validation sets (n = 88) of 3D MRA were built. After preprocessing and data augmentation, a 3D convolutional neural network was trained to estimate each subject's chronological age from in vivo MRA data. There was good correlation between chronological age and predicted age (r = 0.83) in an independent test set (n = 354). The predicted age difference (PAD) of the test set was 2.41 ± 6.22. Interaction term between age and sex was significant for PAD (p = 0.008). After correcting for age and interaction term, men showed higher PAD (p < 0.001). Hypertension was associated with higher PAD with marginal significance (p = 0.073). We suggested that PAD might be a potential measurement of cerebral vascular aging.

Screening Value of Social Frailty and Its Association with Physical Frailty and Disability in Community-Dwelling Older Koreans: Aging Study of PyeongChang Rural Area.

Population aging is a challenge, therefore efficient frailty screening has been increasingly emphasized for mass older populations. This study aimed to evaluate the prevalence of social frailty and its association with physical frailty, geriatric syndromes and activity of daily living (ADL) disability in community-dwelling older adults. A cross-sectional study was conducted with 408 older adults (mean age, 75 years; 58% female) in the Aging Study of PyeongChang Rural Area. A five-item social frailty index was administered (range: 0-5); (1) going out less frequently; (2) rarely visiting the homes of friends; (3) feeling unhelpful to friends and family; (4) being alone; and (5) not talking with someone every day. Social frailty was defined as ≥2 positive responses. Physical frailty was assessed according to the Cardiovascular Health Study frailty phenotype criteria. We used logistic regression to examine whether social frailty can identify older adults with common geriatric syndromes including ADL disability, independently of age, gender, and physical frailty. Social frailty was present in 20.5% (14.5% in male and 25.0% in female) and 11.5% was not overlapped with physical frailty. Social frailty increased risk of ADL disability (odds ratio, 2.53; 95% confidence interval, 1.26-5.09) and depressed mood (odds ratio, 4.01; 95% confidence interval, 1.30-12.39) independently of age, gender, and physical frailty. The predictive power for disability was maximized by using both frailty indices (C statistic 0.73) compared with either frailty index alone (C statistic: 0.71 for social frailty and 0.68 for physical frailty). Social frailty screening is important as it can identify frail older adults who are not captured by demographic characteristics and physical frailty. Moreover, assessment of both social frailty and physical frailty can better detect disability and geriatric syndromes.

Metabolic health is more closely associated with decrease in lung function than obesity.

OBJECTIVE: Previous studies have evaluated the link between metabolic syndrome and obesity with impaired lung function, however findings have been controversial. We aimed to compare lung function among subjects with different metabolic health and obesity status. METHODS: Total 10,071 participants were evaluated at the Health Promotion Center in Seoul St. Mary's Hospital between January 2012 and December 2014. Being metabolically healthy was defined as having fewer than three of the following risk factors: high blood pressure, high fasting blood glucose, high triglyceride, low high-density lipoprotein cholesterol and abdominal obesity. Obesity status was defined as body mass index (BMI) higher than 25 kg/m2. Analyses of pulmonary function were performed in four groups divided according to metabolic health and obesity: metabolically healthy non-obese (MHNO), metabolically health obese (MHO), metabolically unhealthy non-obese (MUHNO), and metabolically unhealthy obese (MUHO). RESULTS: Metabolically unhealthy subjects were more prone to decreased lung function compared with their metabolically healthy counterparts, regardless of obesity status. When multinomial logistic regression analysis was performed according to quartiles of forced vital capacity (FVC) or forced expiratory volume in 1 second (FEV1) (% pred), after adjusting for age, sex, and smoking status, odds ratio (OR) for the lowest FVC and FEV1 (% pred) quartiles were significantly higher in MUHO subjects (1.788 [95% CI, 1.531-2.089] and 1.603 [95% CI, 1.367-1.881]) and lower in MHO subjects (0.768 [95% CI, 0.654-0.902] and 0.826 [95% CI, 0.700-0.976]) with MHNO group as the reference, when OR for highest FVC and FEV1 quartiles were considered as 1.0. CONCLUSION: Metabolic health is more closely associated with impaired lung function than obesity.

Geriatrics Fact Sheet in Korea 2018 From National Statistics.

South Korea is the fastest aging country in the world, having become an aged society in 2017, with over 14% of its population aged 65 years or older. This Korean Geriatrics Fact Sheet 2018 aimed to overview and clarify the current geriatric burden and its trends in South Korea. Using nationwide surveys and public reports from government or related organizations, especially the 2017 Survey of the Living Conditions and Welfare Needs of Korean Older Persons from the Korea Institute for Health and Social Affairs, our committee has summarized the profile, socioeconomic status, health-related lifestyles, geriatric syndromes with major comorbidities, and use of healthcare services in the aging population. We hope that this review will publicize the social burden and seriousness of the aging problem in Korea.

Combination of carboplatin and intermittent normobaric hyperoxia synergistically suppresses benzo[a]pyrene-induced lung cancer.

BACKGROUND/AIMS: We explored the effects of intermittent normobaric hyperoxia alone or combined with chemotherapy on the growth, general morphology, oxidative stress, and apoptosis of benzo[a]pyrene (B[a]P)-induced lung tumors in mice. METHODS: Female A/J mice were given a single dose of B[a]P and randomized into four groups: control, carboplatin (50 mg/kg intraperitoneally), hyperoxia (95% fraction of inspired oxygen), and carboplatin and hyperoxia. Normobaric hyperoxia (95%) was applied for 3 hours each day from weeks 21 to 28. Tumor load was determined as the average total tumor numbers and volumes. Several markers of oxidative stress and apoptosis were evaluated. RESULTS: Intermittent normobaric hyperoxia combined with chemotherapy reduced the tumor number by 59% and the load by 72% compared with the control B[a]P group. Intermittent normobaric hyperoxia, either alone or combined with chemotherapy, decreased the levels of superoxide dismutase and glutathione and increased the levels of catalase and 8-hydroxydeoxyguanosine. The Bax/Bcl-2 mRNA ratio, caspase 3 level, and number of transferase-mediated dUTP nick end-labeling positive cells increased following treatment with hyperoxia with or without chemotherapy. CONCLUSIONS: Intermittent normobaric hyperoxia was found to be tumoricidal and thus may serve as an adjuvant therapy for lung cancer. Oxidative stress and its effects on DNA are increased following exposure to hyperoxia and even more with chemotherapy, and this may lead to apoptosis of lung tumors.

Inhibition of MicroRNA-21 by an antagomir ameliorates allergic inflammation in a mouse model of asthma.

AIM OF THE STUDY: MicroRNA-21 (miR-21) is up-regulated during allergic airway inflammation, reflecting a Th2 immune response. We investigated the effects of an miR-21 antagomir and its mechanism of action in a mouse model of acute bronchial asthma. MATERIALS AND METHODS: BALB/c mice were sensitized and challenged with ovalbumin (OVA). The anti-miR-21 antagomir was administered by intranasal inhalation from the day of sensitization. Changes in cell counts, Th2 cytokine levels in bronchoalveolar (BAL) fluid, and airway hyper-responsiveness (AHR) were examined. Histopathological changes and expression levels of miR-21 in lung tissues were analyzed. The mechanism of action of the antagomir was investigated by counting CD4+/CD8- T cells in splenocytes and by measuring the expression levels of transcription factors associated with T cell polarization. RESULTS: MiR-21 expression was selectively down-regulated in the lung tissues of mice treated with anti-miR-21. The antagomir suppressed AHR compared with that of the OVA-challenged and scrambled RNA-treated groups. It also reduced the total cell and eosinophil counts in BAL fluid and the levels of Th2 cytokines, including IL-4, IL-5, and IL-13. The direct target of miR-21, IL-12p35, was induced in the antagomir-treated group, decreasing the CD4+/CD8- T cell proportions in splenocytes. The levels of transcription factors involved in the Th2-signaling pathway were reduced in lung tissues on treatment with the antagomir. CONCLUSIONS: The miR-21 antagomir suppresses the development of allergic airway inflammation in a mouse model of acute bronchial asthma, inhibiting Th2 activation. These results suggest that this antagomir might be useful for treating bronchial asthma.

Diagnosis of cytomegalovirus pneumonia by quantitative polymerase chain reaction using bronchial washing fluid from patients with hematologic malignancies.

BACKGROUND: The incidence of cytomegalovirus (CMV) pneumonia is increasing in patients diagnosed with hematologic malignancies. The utility of CMV-DNA viral load measurement has not been standardized, and viral cut-off values have not been established. This study was designed to investigate the utility of CMV quantitative real-time PCR (qRT-PCR) using bronchial washing fluid. METHODS: We retrospectively reviewed the microbiologic and pathologic results of bronchial washing fluid and biopsy specimens in addition to the patients' clinical characteristics. RESULTS: A total of 565 CMV qRT-PCR assays were performed using bronchial washing fluid from patients with hematologic malignancies. Among them, 101 were positive for CMV by qRT-PCR; of these, 24 were diagnosed with CMV pneumonia and 70 with CMV infection, and 7 were excluded due to a diagnosis of invasive pulmonary aspergillosis rather than viral pneumonia. The median CMV load determined by qPCR was 1.8 × 105 copies/mL (3.6 103-1.5 × 108) in CMV pneumonia patients and 3.0 × 103 copies/mL (5.0 × 102-1.1 × 105) in those diagnosed with CMV infection (P < 0.01). Using the ROC curve, the optimal inflection points were 18,900 copies/mL (137,970 IU/mL) in post-bone marrow transplantation (BMT) patients, 316,415 copies/mL (2,309,825 IU/mL) in no-BMT patients and 28,774 copies/mL (210,054 IU/mL) in all patients. CONCLUSIONS: The CMV titers in bronchial washing fluid determined by qRT-PCR differed significantly between patients diagnosed with CMV pneumonia and those with CMV infection. The viral cut-off values in bronchial washing fluid were suggested for the diagnosis of CMV pneumonia, which were different depending on the BMT status.

Clinical significance of serum vascular endothelial growth factor in young male asthma patients.

BACKGROUND/AIMS: Vascular endothelial growth factor (VEGF) is an important mediator of angiogenesis. However, little is known about the potential use of serum levels of VEGF as a biomarker for asthma. We investigated the differences in VEGF levels among normal controls, stable asthma patients, and those with exacerbation of acute asthma. All subjects were young males. METHODS: We measured VEGF levels in each patient group, and examined any serial changes in those with acute exacerbation. RESULTS: VEGF levels were significantly higher in stable asthmatic patients and even more so in acute asthmatic patients, compared to healthy controls. However, there was no correlation between VEGF levels and forced expiratory volume in 1 second in patients with stable asthma. In addition, there were no correlations between VEGF levels and asthma control test scores. In patients with acute exacerbation, VEGF levels significantly increased during the acute period; their levels decreased gradually at 7 and 14 days after treatment. CONCLUSIONS: Compared to normal control patients, the serum levels of VEGF were elevated in stable asthma patients and even more elevated in patients with acute exacerbation. However, the role of VEGF as a biomarker in stable asthma is limited. In patients with acute exacerbation, VEGF levels were associated with clinical improvements.

Clinical significance of positive Pneumocystis jirovecii polymerase chain reaction in non-human immunodeficiency virus immunocompromised patients in a real practice.

BACKGROUND/AIMS: Pneumocystis jirovecii polymerase chain reaction (PCR) can be helpful in diagnosing Pneumocystis pneumonia (PCP); however it has limitations. We evaluated the prevalence of positive P. jirovecii PCR from non-human immunodeficiency virus (HIV) immunocompromised patients and tried to determine the risk of PCP development. METHODS: Between May 2009 and September 2012, P. jirovecii PCR was performed in bronchoscopic specimens from 1,231 adult non-HIV immunocompromised patients suspected of respiratory infection. Only 169 patients (13.7%) who were tested positive for P. jirovecii PCR were enrolled. Retrospective chart review was performed. PCP was defined in patients with positive P. jirovecii PCR who were treated for PCP based on the clinical decision. RESULTS: From 169 P. jirovecii PCR-positive patients, 90 patients were in the PCP group (53.3%) and 79 patients were in the non-PCP group (46.7%). In the PCP group, 38% of patients expired or aggravated after therapy, whereas the majority of patients (84%) in the non-PCP group recovered without treatment for PCP. Independent risk factors for PCP by binary logistic regression analysis were underlying conditions- hematological malignancies, solid tumors or solid organ transplantation, dyspnea, age < 60 years, and albumin < 2.9 g/dL. CONCLUSIONS: This study suggests that not all P. jirovecii PCR-positive patients need to be treated for PCP. Among P. jirovecii PCR-positive patients, those who are less than 60 years old, with hematological malignancies, solid tumors or solid organ transplantation, low albumin, and with symptoms of dyspnea, the possibility of PCP might be higher. Treatment should also be selected to these patients.

Different anti-remodeling effect of nilotinib and fluticasone in a chronic asthma model.

BACKGROUND/AIMS: Inhaled corticosteroids are the most effective treatment currently available for asthma, but their beneficial effect against airway remodeling is limited. The tyrosine kinase inhibitor nilotinib has inhibitory activity against c-kit and the platelet-derived growth factor receptor. We compared the effects of fluticasone and nilotinib on airway remodeling in a chronic asthma model. We also examined whether co-treatment with nilotinib and fluticasone had any synergistic effect in preventing airway remodeling. METHODS: We developed a mouse model of airway remodeling, including smooth muscle thickening, in which ovalbumin (OVA)-sensitized female BALB/c-mice were repeatedly exposed to intranasal OVA administration twice per week for 3 months. Mice were treated with fluticasone and/or nilotinib intranasally during the OVA challenge. RESULTS: Mice chronically exposed to OVA developed eosinophilic airway inflammation and showed features of airway remodeling, including thickening of the peribronchial smooth muscle layer. Both fluticasone and nilotinib attenuated airway smooth muscle thickening. However, only nilotinib suppressed fibrotic changes, demonstrating inhibition of collagen deposition. Fluticasone reduced pro-inflammatory cells, such as eosinophils, and several cytokines, such as interleukin 4 (IL-4), IL-5, and IL-13, induced by repeated OVA challenges. On the other hand, nilotinib reduced transforming growth factor ß1 levels in bronchoalveolar lavage fluid and inhibited fibroblast proliferation significantly. CONCLUSIONS: These results suggest that fluticasone and nilotinib suppressed airway remodeling in this chronic asthma model through anti-inflammatory and anti-fibrotic pathways, respectively.

Clinical outcomes of extracorporeal membrane oxygenation support in patients with hematologic malignancies.

BACKGROUND/AIMS: The clinical outcomes of patients with hematologic malignancies who were treated with extracorporeal membrane oxygenation (ECMO) after the failu re of optimal conventional therapy were determined. METHODS: The medical records of all patients administered ECMO during their stay in a medical intensive care unit of Seoul St. Mary's Hospital between February 2010 and July 2013 were reviewed retrospectively. RESULTS: In total, 15 patients with hematologic malignancies were compared to 33 immunocompetent patients with documented cardiorespiratory failure. Underlying hematologic malignancies were significantly associated with lower overall survival (0.0% vs. 24.2%, p = 0.044). Mortality was significantly associated with a higher 24 hours ECMO inspired fraction of oxygen (0.71 ± 0.24 vs. 0.47 ± 0.13, p = 0.015), the development of infection after ECMO (87.5% vs. 25.0%, p = 0.001), and the presence of hyperbilirubinemia (70.0% vs. 0.0%, p < 0.001). Matching of the patients based on their Acute Physiology and Chronic Health Evaluation II scores confirmed the greater risk of mortality in patients with hematologic malignancies (survival: 0.0% vs. 40.0%, p = 0.017). The mean difference in inotropic-equivalent scores after ECMO was significantly lower in the immunocompetent patients than in those with hematologic malignancies (-59.22 ± 97.83 vs. 53.87 ± 164.46, p = 0.026). CONCLUSIONS: Patients with hematologic malignancies who require ECMO for respiratory support have poor outcomes. The incidence of complications in these patients did not significantly differ from that in immunocompetent patients.

Low grade pulmonary lymphomatoid granulomatosis with an endobronchial mass.

Lymphomatoid granulomatosis (LYG) is an angiocentric and angiodestructive neoplastic proliferation of B and T lymphocytes commonly involving the lungs. Epstein-Barr virus is commonly detected in lesional cells. We report a case of a 54-year-old female with underlying monoclonal gammopathy of unknown significance who presented with a 4 week history of dyspnea and cough. Computed tomography scan of the chest showed multiple lung nodules as well as endobronchial narrowing causing atelectasis at the left upper lobe. Bronchoscopic findings revealed obstruction at the lingula segment due to endobronchial mass as a rare presentation. Bronchoscopic biopsy was diagnosed with LYG grade 1. After treatment, the endobronchial mass and lung lesions were completely resolved. However, the patient eventually evolved to malignant lymphoma after 1 year.

An Unusual Presentation of Pulmonary Mucosa-Associated Lymphoid Tissue Lymphoma as Diffuse Pulmonary Infiltrates with Spontaneous Regression.

A 57-year-old woman presented with cough and dyspnea for 2 months. Computed tomography of the chest showed diffuse ground-glass opacities in both lungs. Histologic examination via thoracoscopic lung biopsy revealed atypical lymphoproliferative lesion. Her symptoms and radiologic findings of the chest improved just after lung biopsy without any treatment. Therefore, she was discharged and monitored at an outpatient clinic. Two months later, pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma was confirmed by the detection of API2-MALT1 translocation in fluorescent in situ hybridization analysis. Although the lung lesions resolved spontaneously, she received chemotherapy due to bone marrow involvement in her staging workup. Pulmonary MALT lymphoma is rare. Nodular or consolidative patterns are the most frequent radiologic findings. Although the disease has an indolent growth, it rarely resolves without treatment. We report an unusual case of pulmonary MALT lymphoma with diffuse interstitial abnormalities on image and spontaneous regression on clinical course.

Pneumatosis intestinalis complicated by pneumoperitoneum in a patient with asthma.

Pneumatosis intestinalis (PI) is a very rare condition that is defined as the presence of gas within the subserosal or submucosal layer of the bowel. PI has been described in association with a variety of conditions including gastrointestinal tract disorders, pulmonary diseases, connective tissue disorders, organ transplantation, leukemia, and various immunodeficiency states. We report a rare case of a 74-year-old woman who complained of dyspnea during the management of acute asthma exacerbation and developed PI; but, it improved without any treatment.

Clinical characteristics of asthma combined with COPD feature.

PURPOSE: In clinical practice, some patients with asthma show incompletely reversible airflow obstruction, resembling chronic obstructive pulmonary disease (COPD). The aim of this study was to analyze this overlap phenotype of asthma with COPD feature. MATERIALS AND METHODS: A total of 256 patients, over the age of 40 years or more with a diagnosis of asthma, based on either 1) positive response to bronchodilator: >200 mL forced expiratory volume in 1 s (FEV1) and >12% baseline or 2) positive methacholine or mannitol provocation test, were enrolled. Among the asthma patients, we defined the overlap group with incompletely reversible airflow obstruction [postbronchodilator FEV1/forced vital capacity (FVC)<70] at the initial time of admission and continuing airflow obstruction after at least 3 months follow up. We evaluated clinical features, serum eosinophil counts, serum total immunoglobulin (Ig) E with allergy skin prick test, spirometry, methacholine or mannitol provocation challenges and bronchodilator responses, based on their retrospective medical record data. All of the tests mentioned above were performed within one week. RESULTS: The study population was divided into two groups: asthma only (62%, n=159, postbronchodilator FEV1/FVC≥70) and overlap group (38%, n=97, postbronchodilator FEV1/FVC<70). The overlap group was older, and contained more males and a higher percentage of current or ex-smokers than the asthma only group. Significantly lower FEV1 and higher total lung capacity, functional residual capacity, and residual volume were observed in the overlap group. Finally, significantly lower serum eosinophil count and higher IgE were seen in the overlap group. CONCLUSION: Our results showed that the overlap phenotype was older, male asthmatic patients who have a higher lifetime smoking intensity, more atopy and generally worse lung function.

Blockade of IL-33/ST2 ameliorates airway inflammation in a murine model of allergic asthma.

OBJECTIVE: Interleukin (IL)-33 is involved in the development of lung inflammation by inducing or amplifying Th2 type-mediated responses in various animal models of allergic asthma. The ST2 gene is a member of the IL-1 receptor family, producing a transmembrane form (ST2L) and a soluble secreted form (sST2). sST2 has been shown to block this IL-33/ST2 signaling pathway. This study aimed to investigate whether anti-IL-33 and sST2 reduced airway inflammation in a murine model of asthma. METHODS: BALB/c mice were sensitized and challenged with ovalbumin (OVA), and the effect of sST2 and anti-IL-33 antibody on airway inflammation and airway hyperresponsiveness (AHR) was evaluated. Furthermore, we measured changes in various cytokines in the bronchoalveolar lavage (BAL) fluid when treated with sST2 or anti-IL-33. RESULTS: We observed that anti-IL-33 antibody and sST2 exert a negative regulation on OVA-mediated allergic airway inflammation. Both treatments reduced total cell counts and eosinophil counts in BAL fluid and AHR to methacholine. The Th2 cytokines, such as IL-4, IL-5, and IL-13 in BAL fluid were also significantly decreased after both treatments. However, there were no changes in the level of TGF- ß1 and IL-10 after each treatment. CONCLUSIONS: These results suggest that anti-IL-33 as well as sST2 have therapeutic potential for allergic asthma through inhibition of Th2 cytokine production.